The ectonucleoside triphosphate diphosphatase (E-NTPDase family) of ectonucleotidases includes 8 enzymes: NTPDase1 (encoded by the ENTPD1
gene), NTPDase2 (encoded by the ENTPD2 gene), NTPDase3 (encoded by the ENTPD3 gene), NTPDase4 (encoded by the ENTPD4 gene), NTPDase5 (encoded by the ENTPD5 gene), NTPDase6 (encoded by the ENTPD6 gene), NTPDase7 (encoded by the ENTPD7 gene) and NTPDase8 (encoded by the ENTPD8 gene). NTPDases hydrolyze nucleoside triphosphates and nucleoside diphosphates, producing the corresponding nucleoside monophosphates as final products. Different family members show different specificity for particular nucleotides. NTPDases are involved in various biological processes, such as hemostasis, immune response and development of the nervous system.
The catalytic domain of NTPDases is contained within the loop formed by a cluster of apyrase conserved regions (ACRs). All family members require divalent cations, such as calcium (Ca2+) or magnesium (Mg2+) ions, for catalytic activity. The hydrolysis involves a nucleophilic attack of a water molecule on the terminal phosphate of a nucleotide substrate.
All E-NTPDase family members are transmembrane proteins, associated with either plasma membrane (NTPDase1, NTPDase2, NTPDase3 and NTPDase8) or organelle membranes (NTPDase4 and NTPDase7). Two family members, NTPDase5 and NTPDase6, can be secreted into extracellular space following a proteolytic cleavage from the plasma membrane. NTPDases hydrolyze exocytoplasmic nucleotides, thus regulating the availability of ligands for purinergic receptors. Glycosylation and oligomerization are involved in the regulation of NTPDases, but have not been thoroughly studied.
For reviews of the NTPDase family, please refer to Robson et al. 2006 and Zimmermann et al. 2012.